Recent studies have identified two responses from proximal retina of the cat not previously observed in mammals: a light-adapted response - the M-wave, and a dark-adapted response termed the scotopic threshold response (STR). These responses can be used to study proximal retinal function and there is evidence that they contribute to the flash ERG and pattern ERG (PERG). Our goals are to obtain a clearer understanding of the cellular mechanisms of these responses and to determine how they contribute to the flash and pattern ERG. Specific experiments will (1) characterize and differentiate the M-wave and STR with regard to rod vs cone contributions, effect of retinal eccentricity, and spatial and temporal frequency response; (2) investigate the mechanisms of these responses in terms of a potassium mediated Muller cell hypothesis of their origin and the retinal circuits that contribute to the changes in (K+)o; (3) evaluate the amplitude and polarity of the contributions of the M-wave to the photopic flash ERG and the PERG; (4) evaluate the contribution of the STR to the scotopic flash ERG. The method will be to record intraretinally in the cat with microelectrodes and K+-sensitive microelectrodes, and also to record the flash and pattern ERG from the vitreous. The quantitative techniques previously applied to retinal ganglion cells for measuring spatial and temporal frequency response and characterizing the linear and nonlinear response mechanisms will be used. Selected pharmacological agents known to effect proximal retinal synaptic transmission, spike discharge, K+ conductance, glial cells, and on and off circuits will be utilized to test the Muller cell hypothesis, to investigate the retinal circuitry, and to assess the contribution of the STR to the flash ERG, and the M-wave to the flash and PERG. It has long been thought that the waves of the mammalian ERG within 2-3 seconds after onset of illumination all originate in distal retina. There is increasing evidence that currents from proximal retina also contribute to the initial portion of the ERG, and to the PERG. There is sufficient similarity between human and cat ERG and PERG to indicate that the present studies of proximal retina will enhance our understanding of the origin of human responses and, hopefully increase their clinical value, particularly for diagnosing and following diseases affecting proximal retina.